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Low Bone Formation in Premenopausal Women with Idiopathic Osteoporosis

Department of Medicine (M.A.D., D.J.M., J.F., E.S.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; and Regional Bone Center (D.D., H.Z.), Helen Hayes Hospital, West Haverstraw, New York 10993

Address all correspondence and requests for reprints to: Elizabeth Shane, M.D., Columbia University, College of Physicians & Surgeons, Department of Medicine, PH8W-864, 630 West 168th Street, New York, New York. E-mail: es54{at}columbia.edu.

Most young people with osteoporosis have an identifiable cause. Others have an idiopathic form for which no etiology can be found. We have reported that men with idiopathic osteoporosis (IOP) have histomorphometric evidence of decreased bone formation and osteoblast dysfunction. The pathogenesis of IOP in young women remains unclear. Our aim was to characterize the histomorphometry of IOP in healthy premenopausal women. We compared iliac crest bone biopsies from nine women with IOP to 18 healthy, age-, sex-, and race-matched controls. Compared with controls, differences in bone remodeling were identified, particularly in cancellous bone. Although cancellous bone volume did not differ, there was a trend toward lower trabecular number and increased separation in women with IOP. In cancellous bone, there was no increase in osteoid width or perimeter, but IOP patients had lower bone formation parameters, including a 10% reduction in wall width (P < 0.01), an 18% reduction in mineral apposition rate (P < 0.01), and a 42% reduction in mineralized perimeter (P 0.02). Additionally, the bone formation rate was 52% lower (0.026 ± 0.004 vs. 0.054 ± 0.01 µm/µm²·d; P < 0.01), and a trend toward decreased activation frequency was observed in IOP patients. Conversely, bone resorption was altered in IOP patients, reflected by a longer resorption period (134 ± 35 vs. 38 ± 6 d; P 0.02) and increased eroded perimeter (5.5 ± 0.7 vs. 4.1 ± 0.4%; P = 0.05). Wall width and mineralized perimeter were similarly lower in endocortical bone. Resorption period and eroded perimeter were higher in intracortical bone. Women with IOP have uncoupling of resorption and formation and, like men with IOP, osteoblast dysfunction.